Nonetheless, PS48 restored Akt and GSK phosphorylations in the hippocampus of HFD-fed mice as shown in Figure 1B,C and Figure 5A. One possibility for the curious disparity in hippocampal neuroprotection by PS48 is that TG animals on an HFD had greater vasculopathy and/or inflammation burden [57,58], rendering Tau phosphorylation and neuronal loss less responsive to drugs. Here, MAPT is linked to vascular disorder.